Hyperbaric Oxygen Therapy (HBOT) and Its Correlation with Female Infertility: A Systematic Review and Meta-Analysis

Importance: Infertility is a widespread problem and the scientific world is constantly looking for possible solutions that can increase the chances of a pregnancy. Objective: We perform a systematic review with meta-analysis to compare the different current intervention methodologies to treat female infertility with hyperbaric oxygen therapy (HBOT). This review also introduces the molecular theoretical hypothesis of how the use of HBOT could regulate the expression of sirtuins, in particular, SIRT1 through the well-known hyperoxia-hypoxia paradox. Data sources: We performed research among the results of the major electronic databases (Cochrane, Lilacs, Scopus, Pubmed) and internet search engines (Google, Google Scholar) for studies that evaluated the correlation between female infertility and HBOT. Study selection and synthesis: Studies that match the following criteria were included: (1) every type of published or ongoing study on specified databases dealing with (a) female infertility of every cause and (b) hyperbaric oxygen therapy or (c) oxygen therapy linked. Thanks to the analysis of the various observational and non-observational studies, we try to answer some questions considered relevant to the topic based on Evidence-Based Medicine (EBM). The program used here to produce the following methodological review is Cochrane Review Manager 5.4. Then, the review was checked and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (www.prisma-statement.org). Meta-analysis was performed using the ‘metan’ routine by the Stata statistics software (version 13 for Windows Stata Corporation, 2016). The evaluation of evidence and risk of bias assessment was done with the GRADEpro tool, available at https://gdt.gradepro.org/. Main outcome(s): Association between HBOT and female infertility. Results: Included articles and methodology are specified in the article. A significant change in endometrial thickness was observed in the meta-analysis, the SMD was 1.388, p<0.001. No difference in conceived with HBO therapy (versus no HBO therapy) was observed in the meta-analysis, RR=1.149, p=0.827. Conclusion and relevance: The studies present in the literature, despite the vast heterogeneity, suggest that there is a possible link between HBOT and female infertility. However, more studies are needed to evaluate this new link in the management and possible treatment of women with infertility.